Protease inhibitory activities directed against both a serine protease (trypsin) and a thiol protease (papain) have been observed in human tears. Inhibitory activities are also found in skin and in other external secretions such as genital secretions, saliva, urine, and lung mucus. Protease inhibitors in the lung appear to protect this tissue from breakdown by degradative enzymes released by leukocytes responding to an inflammatory stimulus. Exogenous protease inhibitors have been shown to play a role in corneal wound healing and corneal vascularization but there have been no studies of the effects of endogenous inhibitors. We propose to further purify and characterize the protease inhibitors found in tears and to determine the role of these inhibitors in ocular health and disease. We will look at tears from laboratory animals and we will examine lacrimal glands to see if inhibitory activity can be found in these glands. Purification techniques will be developed. We will establish normal inhibitor concentrations in tears and determine whether there are variations which correlate with age, sex, time of day, or general state of health. We will then examine inhibitor levels in ocular inflammations due to both immunological and microbial factors and in corneal wound healing. From these studies we expect to be able to determine the function of tear inhibitors in maintenance of ocular health.